Weight loss in head and neck cancer patients little noticed in general practice

INTRODUCTION: In head and neck cancer patients, weight loss increases morbidity and mortality, and decreases treatment tolerance and quality of life. Early nutritional intervention has beneficial effects on these factors. AIM: We observed patients’ weight courses after specialists’ care and surveyed nutrition-related documentation by general practitioners (GPs). METHODS: From a Head and Neck Oncology Centre (HNOC) study, 68 patients were asked to participate in an extended general practice cohort. Twenty-six patients participated in the prospective three-monthly weight measurements during the year after HNOC care. We extracted nutritional information contained in referral letters (n=24) and medical records from the year before referral (n=45) and after HNOC care (n=26). An impaired nutritional status was assigned to weight loss =10% within six months or Body Mass Index (BMI

eFLINT: a domain-specific language for executable norm specifications

Software systems that share potentially sensitive data are subjected to laws, regulations, policies and/or contracts. The monitoring, control and enforcement processes applied to these systems are currently to a large extent manual, which we rather automate by embedding the processes as dedicated and adaptable software services in order to improve efficiency and effectiveness. This approach requires such regulatory services to be closely aligned with a formal description of th

Genomic Prediction with 12.5 Million SNPs for 5503 Holstein Friesian Bulls

This study reports the first preliminary results of genomic prediction with whole-genome sequence data (12,590,056 SNPs) for 5503 bulls with accurate phenotypes. Two methods were compared: genome-enabled best linear unbiased prediction (GBLUP) and a Bayesian approach (BSSVS). Results were compared with results using BovineHD genotypes (631,428 SNPs). Results were reported for somatic cell score, interval between first and last insemination, and protein yield. For all traits, and both methods genomic prediction with sequence data showed similar results compared to BovineHD and GBLUP showed similar results compared to BSSVS. However, it remains to be seen if reliability of BSSVS with sequence data will improve after more sampling cycles have been finished

Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature

Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD.'' All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations

Both SEPT2 and MLL are down-regulated in MLL-SEPT2 therapy-related myeloid neoplasia

<p>Abstract</p> <p>Background</p> <p>A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in <it>MLL</it>-related leukemia. Recently, we have established the <it>MLL-SEPT2 </it>gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified <it>MLL </it>and <it>SEPT2 </it>gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of <it>MLL-SEPT2</it>-associated myeloid neoplasms so far described in the literature.</p> <p>Methods</p> <p>Cytogenetics, fluorescence in situ hybridization (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the major AML genetic subgroups: <it>CBFB-MYH11 </it>(n = 13), <it>PML-RARA </it>(n = 12); <it>RUNX1-RUNX1T1 </it>(n = 12), normal karyotype (n = 11), and <it>MLL </it>gene fusions other than <it>MLL-SEPT2 </it>(n = 10). We also studied all three <it>MLL-SEPT2 </it>myeloid neoplasia cases reported in the literature, namely two AML patients and a t-MDS patient.</p> <p>Results</p> <p>When compared with normal controls, we found a 12.8-fold reduction of wild-type <it>SEPT2 </it>and <it>MLL-SEPT2 </it>combined expression in cases with the <it>MLL-SEPT2 </it>gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of wild-type <it>MLL </it>and <it>MLL-SEPT2 </it>combined expression (p = 0.028). The down-regulation of <it>SEPT2 </it>in <it>MLL-SEPT2 </it>myeloid neoplasias was statistically significant when compared with all other leukemia genetic subgroups (including those with other <it>MLL </it>gene fusions). In addition, <it>MLL </it>expression was also down-regulated in the group of <it>MLL </it>fusions other than <it>MLL-SEPT2</it>, when compared with the normal control group (p = 0.023)</p> <p>Conclusion</p> <p>We found a significant down-regulation of both <it>SEPT2 </it>and <it>MLL </it>in <it>MLL-SEPT2 </it>myeloid neoplasias. In addition, we also found that <it>MLL </it>is under-expressed in AML patients with <it>MLL </it>fusions other than <it>MLL-SEPT2</it>.</p

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

Patient recall of receiving lifestyle advice for overweight and hypertension from their General Practitioner

BackgroundOverweight, obesity and hypertension can be prevented through improvements in lifestyle including nutrition and physical activity. General practitioners (GPs) in Australia have access to over 90% of the population in the course of a year and therefore, the general practice setting may be ideal to assist patients with lifestyle change for weight management and hypertension. The present study aimed to determine the proportion of overweight/obese patients that recalled receiving advice by their GP to make lifestyle changes for weight loss. Recall of advice received by hypertensive patients to reduce salt intake was also measured.MethodsA face to face survey was conducted on a representative sample (urban, suburban and rural) of South Australian residents. Respondents provided information on height and weight (self-report), whether they had received lifestyle advice from their GP for weight loss, and for those with self reported hypertension if they had received advice to reduce dietary salt.ResultsThe sample included 2947 South Australian adult residents (58% female; BMI (mean (SD)), 26.6 (5.3) kg/m2; age, 50.7 (18.0) years). Ninety-six percent had visited their GP in the past 12 months. Forty-one percent of males and 25% of females were overweight and 19% of males and 20% of females were obese. Twenty-seven percent of overweight/obese respondents reported receiving lifestyle advice for weight loss purposes. Of the 33% who reported they had hypertension, 34% reported receiving advice to reduce salt intake.ConclusionsLess than 1/3 of overweight/obese patients reported that they had received lifestyle advice that could assist with weight loss from their GP. About a third of respondents with hypertension reported that they received advice to reduce salt intake. There are potentially missed opportunities in which GPs could provide re-enforcement of benefits of lifestyle changes with respect to weight and blood pressure control.<br /